scholarly journals Development aggravates the severity of skeletal muscle catabolism induced by endotoxemia in neonatal pigs

2012 ◽  
Vol 302 (6) ◽  
pp. R682-R690 ◽  
Author(s):  
Renán A. Orellana ◽  
Agus Suryawan ◽  
Fiona A. Wilson ◽  
María C. Gazzaneo ◽  
Marta L. Fiorotto ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Degradation ◽  
Muscle Protein ◽  
Age Groups ◽  
Full Length ◽  
Protein Catabolism ◽  
Neonatal Pigs ◽  
Accretion Rates ◽  
Pkb Phosphorylation ◽  
Signal Activation

Accretion rates of muscle protein are elevated in normal neonates, but this anabolic drive decreases with maturation. As this change occurs, it is not known whether development also influences muscle protein catabolism induced by sepsis. We hypothesize that protein degradation in skeletal muscle induced by endotoxemia becomes more severe as the neonate develops. Fasted 7- and 26-day-old pigs were infused for 8 h with LPS (0 and 10 μg·kg−1·h−1), while plasma amino acids (AA), 3-methylhistidine (3-MH), and α-actin concentrations and muscle protein degradation signal activation were determined ( n = 5–7/group/age). Plasma full-length α-actin was greater in 7- than 26-day-old pigs, suggesting a higher baseline protein turnover in neonatal pigs. LPS increased plasma total AA, 3-MH, and full-length and cleaved α-actin in 26- than in 7-day-old pigs. In muscle of both age groups, LPS increased AMPK and NF-κB phosphorylation, the abundances of activated caspase 3 and E-3 ligases MuRF1 and atrogin1, as well as the abundance of cleaved α-actin, suggesting activation of muscle proteolysis by endotoxin in muscle. LPS decreased Forkhead box 01 (Fox01) and Fox04 phosphorylation and increased procaspase 3 abundance in muscle of 26-day-old pigs despite the lack of effect of LPS on PKB phosphorylation. The results suggest that skeletal muscle in healthy neonatal pigs maintains high baseline degradation signal activation that cannot be enhanced by endotoxin, but as maturation advances, the effect of LPS on muscle protein catabolism manifests its severity.

scholarly journals Aging and acute exercise enhance free radical generation in rat skeletal muscle

1999 ◽  
Vol 87 (1) ◽  
pp. 465-470 ◽  
Author(s):  
J. Bejma ◽  
L. L. Ji
Keyword(s):  
Skeletal Muscle ◽  
Lipid Peroxidation ◽  
Acute Exercise ◽  
Muscle Protein ◽  
Vastus Lateralis ◽  
Age Groups ◽  
Protein Carbonyl ◽  
Biological Aging ◽  
Young Rats ◽  
Old Rats

Reactive oxygen species (ROS) are implicated in the mechanism of biological aging and exercise-induced oxidative damage. The present study examined the effect of an acute bout of exercise on intracellular ROS production, lipid and protein peroxidation, and GSH status in the skeletal muscle of young adult (8 mo, n = 24) and old (24 mo, n = 24) female Fischer 344 rats. Young rats ran on a treadmill at 25 m/min and 5% grade until exhaustion (55.4 ± 2.7 min), whereas old rats ran at 15 m/min and 5% grade until exhaustion (58.0 ± 2.7 min). Rate of dichlorofluorescin (DCFH) oxidation, an indication of ROS and other intracellular oxidants production in the homogenate of deep vastus lateralis, was 77% ( P < 0.01) higher in rested old vs. young rats. Exercise increased DCFH oxidation by 38% ( P < 0.09) and 50% ( P < 0.01) in the young and old rats, respectively. DCFH oxidation in isolated deep vastus lateralis mitochondria with site 1 substrates was elevated by 57% ( P < 0.01) in old vs. young rats but was unaltered with exercise. Significantly higher DCFH oxidation rate was also found in aged-muscle mitochondria ( P < 0.01), but not in homogenates, when ADP, NADPH, and Fe3+ were included in the assay medium without substrates. Lipid peroxidation in muscle measured by malondialdehyde content showed no age effect, but was increased by 20% ( P < 0.05) with exercise in both young and old rats. Muscle protein carbonyl formation was unaffected by either age or exercise. Mitochondrial GSH/ GSSG ratio was significantly higher in aged vs. young rats ( P < 0.05), whereas exercise increased GSSG content and decreased GSH/GSSG in both age groups ( P < 0.05). These data provided direct evidence that oxidant production in skeletal muscle is increased in old age and during prolonged exercise, with both mitochondrial respiratory chain and NADPH oxidase as potential sources. The alterations of muscle lipid peroxidation and mitochondrial GSH status were consistent with these conclusions.

Protein-tyrosine-phosphatase 1B activation is regulated developmentally in muscle of neonatal pigs

2003 ◽  
Vol 284 (1) ◽  
pp. E47-E54 ◽  
Author(s):  
Agus Suryawan ◽  
Teresa A. Davis
Keyword(s):  
Skeletal Muscle ◽  
Insulin Receptor ◽  
Signaling Pathway ◽  
Tyrosine Phosphorylation ◽  
Insulin Signaling ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Age Groups ◽  
Protein Tyrosine Phosphatase 1B ◽  
Neonatal Pigs

The high activity of the insulin-signaling pathway contributes to the enhanced feeding-induced stimulation of translation initiation in skeletal muscle of neonatal pigs. Protein-tyrosine-phosphatase 1B (PTP1B) is a negative regulator of the tyrosine phosphorylation of the insulin receptor (IR) and insulin receptor substrate 1 (IRS-1). The activity of PTP1B is determined mainly by its association with IR and Grb2. We examined the level of PTP1B activity, PTP1B protein abundance, PTP1B tyrosine phosphorylation, and the association of PTP1B with IR and Grb2 in skeletal muscle and liver of fasted and fed 7- and 26-day-old pigs. PTP1B activity in skeletal muscle was lower (P < 0.05) in 7- compared with 26-day-old pigs but in liver was similar in the two age groups. PTP1B abundances were similar in muscle but lower (P < 0.05) in liver of 7- compared with 26-day-old pigs. PTP1B tyrosine phosphorylation in muscle was lower (P < 0.05) in 7- than in 26-day-old pigs. The associations of PTP1B with IR and with Grb2 were lower (P < 0.05) at 7 than at 26 days of age in muscle, but there were no age effects in liver. Finally, in both age groups, fasting did not have any effect on these parameters. These results indicate that basal PTP1B activation is developmentally regulated in skeletal muscle of neonatal pigs, consistent with the developmental changes in the activation of the insulin-signaling pathway reported previously. Reduced PTP1B activation in neonatal muscle likely contributes to the enhanced insulin sensitivity of skeletal muscle in neonatal pigs.

Developmental changes in the feeding-induced activation of the insulin-signaling pathway in neonatal pigs

2001 ◽  
Vol 281 (5) ◽  
pp. E908-E915 ◽  
Author(s):  
Agus Suryawan ◽  
Hanh V. Nguyen ◽  
Jill A. Bush ◽  
Teresa A. Davis
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Insulin Receptor ◽  
Insulin Signaling ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Skeletal Muscle Protein ◽  
Neonatal Pigs ◽  
Skeletal Muscle Protein Synthesis ◽  
Primary Determinant

In neonatal animals, feeding stimulates skeletal muscle protein synthesis, a response that declines with development. Both the magnitude of the feeding response and its developmental decline can be reproduced by insulin infusion, suggesting that an altered responsiveness to insulin is a primary determinant of the developmental decline in the stimulation of protein synthesis by feeding. In this study, 7- and 26-day-old pigs were either fasted overnight or fed porcine milk after an overnight fast. We examined the abundance and degree of tyrosine phosphorylation of the insulin receptor (IR), insulin receptor substrate-1 (IRS-1), and IRS-2 in skeletal muscle and, for comparison, liver. We also evaluated the association of IRS-1 and IRS-2 with phosphatidylinositol 3-kinase (PI 3-kinase). The abundance of IR protein in muscle was twofold higher at 7 than at 26 days, but IRS-1 and IRS-2 abundances were similar in muscle of 7- and 26-day-old pigs. The feeding-induced phosphorylations were greater at 7 than at 26 days of age for IR (28- vs. 13-fold), IRS-1 (14- vs. 8-fold), and IRS-2 (21- vs. 12-fold) in muscle. The associations of IRS-1 and IRS-2 with PI 3-kinase were also increased by refeeding to a greater extent at 7 than at 26 days (9- vs. 5-fold and 6- vs. 4-fold, respectively). In liver, the abundance of IR, IRS-1, and IRS-2 was similar at 7 and 26 days of age. Feeding increased the activation of IR, IRS-1, IRS-2, and PI 3-kinase in liver only twofold, and these responses were unaffected by age. Thus our findings demonstrate that the feeding-induced activation of IR, IRS-1, IRS-2, and PI 3-kinase in skeletal muscle decreases with development. Further study is needed to ascertain whether the developmental decline in the feeding-induced activation of early insulin-signaling components contributes to the developmental decline in translation initiation in skeletal muscle.

Total and net muscle protein breakdown in infection determined by amino acid effluxes

1990 ◽  
Vol 258 (5) ◽  
pp. E856-E863 ◽  
Author(s):  
J. Sjolin ◽  
H. Stjernstrom ◽  
G. Friman ◽  
J. Larsson ◽  
J. Wahren
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Urinary Excretion ◽  
Protein Degradation ◽  
Muscle Protein ◽  
Human Infection ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Skeletal Muscle Protein ◽  
Mild Disease

The present investigation was undertaken to study whether, in human infection of varying severity, peripheral 3-methylhistidine efflux and urinary excretion are associated with net protein degradation and to estimate the protein synthesis rate from the combined effluxes of 3-methylhistidine, tyrosine, and phenylalanine. Quadruplicate femoral arteriovenous differences of 3-methylhistidine, tyrosine, and phenylalanine were multiplied by leg plasma flow in 15 infected patients. Leg effluxes for 3-methylhistidine, tyrosine, and phenylalanine were -0.074 +/- 0.011, -2.57 +/- 0.43, and -3.17 +/- 0.44 mumol/min, respectively. There was a significant linear relationship (P less than 0.01) between the effluxes of tyrosine and phenylalanine and the efflux and urinary excretion of 3-methylhistidine. A significant release of tyrosine and phenylalanine was observed in patients studied at the 3-methylhistidine level seen in normal healthy subjects. It is concluded that in infection 1) there is an increased breakdown of skeletal muscle protein and a reduced rate of protein synthesis, with the latter being relatively more important in patients with mild disease; and 2) urinary 3-methylhistidine excretion is associated with net skeletal muscle protein degradation for the patient group studied.

Physiological rise in plasma leucine stimulates muscle protein synthesis in neonatal pigs by enhancing translation initiation factor activation

2005 ◽  
Vol 288 (5) ◽  
pp. E914-E921 ◽  
Author(s):  
Jeffery Escobar ◽  
Jason W. Frank ◽  
Agus Suryawan ◽  
Hanh V. Nguyen ◽  
Scot R. Kimball ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mrna Translation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Neonatal Pigs ◽  
Plasma Leucine

Protein synthesis in skeletal muscle of adult rats increases in response to oral gavage of supraphysiological doses of leucine. However, the effect on protein synthesis of a physiological rise in plasma leucine has not been investigated in neonates, an anabolic population highly sensitive to amino acids and insulin. Therefore, in the current study, fasted pigs were infused intra-arterially with leucine (0, 200, or 400 μmol·kg−1·h−1), and protein synthesis was measured after 60 or 120 min. Protein synthesis was increased in muscle, but not in liver, at 60 min. At 120 min, however, protein synthesis returned to baseline levels in muscle but was reduced below baseline values in liver. The increase in protein synthesis in muscle was associated with increased plasma leucine of 1.5- to 3-fold and no change in plasma insulin. Leucine infusion for 120 min reduced plasma essential amino acid levels. Phosphorylation of eukaryotic initiation factor (eIF)-4E-binding protein-1 (4E-BP1), ribosomal protein (rp) S6 kinase, and rpS6 was increased, and the amount of eIF4E associated with its repressor 4E-BP1 was reduced after 60 and 120 min of leucine infusion. No change in these biomarkers of mRNA translation was observed in liver. Thus a physiological increase in plasma leucine stimulates protein synthesis in skeletal muscle of neonatal pigs in association with increased eIF4E availability for eIF4F assembly. This response appears to be insulin independent, substrate dependent, and tissue specific. The results suggest that the branched-chain amino acid leucine can act as a nutrient signal to stimulate protein synthesis in skeletal muscle of neonates.

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